Hypertrophy of the Heart

Abstract

Abstract-Recent studies call into question the necessity of hypertrophic growth of the heart as a "compensatory" response to hemodynamic stress. These findings, coupled with recent progress in dissecting the molecular bases of hypertrophy, raise the prospect of suppressing hypertrophy without provoking circulatory insufficiency. In this article, we focus on signaling pathways that hold promise as potential targets for therapeutic intervention. We also summarize observations from animal models and clinical trials that suggest benefit from an antihypertrophic strategy. Key Words: hypertrophy Ⅲ heart failure Ⅲ signal transduction C ardiac hypertrophy is an adaptive response to pressure or volume stress, mutations of sarcomeric (or other) proteins, or loss of contractile mass from prior infarction. Hypertrophic growth accompanies many forms of heart disease, including ischemic disease, hypertension, heart failure, and valvular disease. In these types of cardiac pathology, pressure overload-induced concentric hypertrophy is believed to have a compensatory function by diminishing wall stress and oxygen consumption. 1-3 At the same time, ventricular hypertrophy is associated with significantly increased risk of heart failure and malignant arrhythmia. 4,5 In the 1960s, Meerson and colleagues 6 divided hypertrophic transformation of the heart into 3 stages: (1) developing hypertrophy, in which load exceeds output, (2) compensatory hypertrophy, in which the workload/mass ratio is normalized and resting cardiac output is maintained, and (3) overt heart failure, with ventricular dilation and progressive declines in cardiac output despite continuous activation of the hypertrophic program. The late-phase "remodeling" process that leads to failure is associated with functional perturbations of cellular Ca 2ϩ homeostasis 7 and ionic currents, 8,9 which contribute to an adverse prognosis by predisposing to ventricular dysfunction and malignant arrhythmia. Significant morphological changes include increased rates of apoptosis, 10 fibrosis, and chamber dilation. Even though the dichotomy between adaptive and maladaptive hypertrophy has been appreciated for more than a century, 11 mechanisms that determine how long-standing hypertrophy ultimately progresses to overt heart failure are poorly understood.At the cellular level, cardiomyocyte hypertrophy is characterized by an increase in cell size, enhanced protein synthesis, and heightened organization of the sarcomere.Classically, 2 different hypertrophic phenotypes can be distinguished: (1) concentric hypertrophy due to pressure overload, which is characterized by parallel addition of sarcomeres and lateral growth of individual cardiomyocytes, and (2) eccentric hypertrophy due to volume overload or prior infarction, characterized by addition of sarcomeres in series and longitudinal cell growth. 12 At the molecular level, these changes in cellular phenotype are accompanied by reinduction of the so-called fetal gene program, because patterns of gene expression mimic those seen during ...

Evaluation of non‐Gaussian diffusion in cardiac MRI

“…This could be particularly relevant in disease states such as hypertrophy, in which proliferation and enlargement of cardiomyocytes leads to changes in the distribution of cellular restrictions to water diffusion 21. Transverse aortic constriction (TAC) is widely used to surgically generate animal models of heart failure 22.…”

Extracellular high‐mobility group box 1 mediates pressure overload‐induced cardiac hypertrophy and heart failure

“…Cardiac hypertrophy, which may eventually trigger the transition to heart failure, occurs in many forms of clinical conditions, including hypertension and valvular heart disease 1, 2. Although it is widely accepted that inflammation including various cytokines and receptors are involved in the pathological process of pressure overload‐induced cardiac hypertrophy and cardiac dysfunction 3, 4, 5, the molecular mechanisms underlying the progression of cardiac hypertrophy and succedent heart failure have not yet been completely defined.…”

Angiotensin‐Converting Enzyme 3 (ACE3) Protects Against Pressure Overload‐Induced Cardiac Hypertrophy

“…Pathological hypertrophy is ultimately a detrimental process that is associated with malignant arrhythmia and heart failure 1. Therefore, identifying efficient targets to suppress of maladaptive hypertrophy may be a useful therapeutic strategy to prevent heart failure and other heart related diseases.…”

“…Cardiac hypertrophy develops as an adaptive response to an increased workload induced by diverse pathological stimuli, eg, hypertension, aortic stenosis, and valvular diseases 1. Cardiac hypertrophy is usually characterized by the enlargement of cardiomyocytes, an increase in protein synthesis, the reorganization of sarcomeres and the reactivation of the fetal gene program.…”